Objective: To assess the feasibility of endovascular thrombectomy (EVT) for the treatment of acute ischemic stroke (AIS) in children. Methods: Clinical data and follow-up information of 4 AIS children who received EVT in the Department of Intervention & Hemangioma at the Children's Hospital of the Capital Institute of Pediatrics from December 2020 to June 2021 were collected retrospectively. The vascular recanalization after EVT was assessed by the modified thrombolysis in cerebral infarction (mTICI) score. Efficacy outcomes were assessed with initial and postprocedural Pediatric National Institutes of Health Stroke Scale (PedNIHSS) score, and the modified Rankin scale (mRS) score at 3 and 6 months after treatment. Safety assessments included perioperative complications and intracranial hemorrhage post-treatment. Results: A total of 5 EVT treatment were performed on 4 children with AIS, of whom 3 were male. The age of onset was 4.6, 13.8, 7.8, 8.0, 8.9 years, respectively. The time from symptom onset to initiation of EVT was 19.0, 25.0, 22.0, 4.0, 16.5 hours, respectively and all patients achieved successful recanalization of the vessel after EVT (mTICI≥2b). The PedNIHSS score was 39, 14, 25, 39, 24 before treatment and decreased to 8, 1, 12, 39, 5 at discharge. All the procedures were performed with no perioperative complications. Only 1 patient with congenital heart disease had a recurrent AIS with malignant brain oedema and brain hernia. Although the occluded vessels were successfully recanalized,the symptoms were not improved and this patient died after treatment abandonment. The other 3 patients achieved good recovery at 6 months postoperatively. The mRS score of 3 patients was 3, 1, 2 at 3 months after EVT and decreased to 2, 1, 1 at 6 months. Conclusion: EVT treatment may be feasible and safe for pediatric AIS due to large vessel occlusion even when the treatment was initiated 6 hours post stroke, but children with heart disease may have a dismal prognosis.
United States ; Humans ; Child ; Male ; Female ; Ischemic Stroke ; Retrospective Studies ; Thrombectomy ; Brain ; Stroke/therapy*

Objective: Total neoadjuvant therapy has been used to improve tumor responses and prevent distant metastases in patients with locally advanced rectal cancer (LARC). Patients with complete clinical responses (cCR) then have the option of choosing a watch and wait (W&W) strategy and organ preservation. It has recently been shown that hypofractionated radiotherapy has better synergistic effects with PD-1/PD-L1 inhibitors than does conventionally fractionated radiotherapy, increasing the sensitivity of microsatellite stable (MSS) colorectal cancer to immunotherapy. Thus, in this trial we aimed to determine whether total neoadjuvant therapy comprising short-course radiotherapy (SCRT) combined with a PD-1 inhibitor improves the degree of tumor regression in patients with LARC. Methods: TORCH is a prospective, multicenter, randomized, phase II trial (TORCH Registration No. NCT04518280). Patients with LARC (T3-4/N+M0, distance from anus ≤10 cm) are eligible and are randomly assigned to consolidation or induction arms. Those in the consolidation arm receive SCRT (25Gy/5 Fx), followed by six cycles of toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Those in the induction arm receive two cycles of ToriCAPOX, then undergo SCRT, followed by four cycles of ToriCAPOX. Patients in both groups undergo total mesorectal excision (TME) or can choose a W&W strategy if cCR has been achieved. The primary endpoint is the complete response rate (CR, pathological complete response [pCR] plus continuous cCR for more than 1 year). The secondary endpoints include rates of Grade 3-4 acute adverse effects (AEs) etc. Results: Up to 30 September 2022, 62 patients attending our center were enrolled (Consolidation arm: 34, Induction arm:28). Their median age was 53 (27-69) years. Fifty-nine of them had MSS/pMMR type cancer (95.2%), and only three MSI-H/dMMR. Additionally, 55 patients (88.7%) had Stage III disease. The following important characteristics were distributed as follows: lower location (≤5 cm from anus, 48/62, 77.4%), deeper invasion by primary lesion (cT4 7/62, 11.3%; mesorectal fascia involved 17/62, 27.4%), and high risk of distant metastasis (cN2 26/62, 41.9%; EMVI+ 11/62, 17.7%). All 62 patients completed the SCRT and at least five cycles of ToriCAPOX, 52/62 (83.9%) completing six cycles of ToriCAPOX. Finally, 29 patients achieved cCR (46.8%, 29/62), 18 of whom decided to adopt a W&W strategy. TME was performed on 32 patients. Pathological examination showed 18 had achieved pCR, four TRG 1, and 10 TRG 2-3. The three patients with MSI-H disease all achieved cCR. One of these patients was found to have pCR after surgery whereas the other two adopted a W&W strategy. Thus, the pCR and CR rates were 56.2% (18/32) and 58.1% (36/62), respectively. The TRG 0-1 rate was 68.8% (22/32). The most common non-hematologic AEs were poor appetite (49/60, 81.7%), numbness (49/60, 81.7%), nausea (47/60, 78.3%) and asthenia (43/60, 71.7%); two patients did not complete this survey. The most common hematologic AEs were thrombocytopenia (48/62, 77.4%), anemia (47/62, 75.8%), leukopenia/neutropenia (44/62, 71.0%) and high transaminase (39/62, 62.9%). The main Grade III-IV AE was thrombocytopenia (22/62, 35.5%), with three patients (3/62, 4.8%) having Grade IV thrombocytopenia. No Grade V AEs were noted. Conclusions: SCRT-based total neoadjuvant therapy combined with toripalimab can achieve a surprisingly good CR rate in patients with LARC and thus has the potential to offer new treatment options for organ preservation in patients with MSS and lower-location rectal cancer. Meanwhile, the preliminary findings of a single center show good tolerability, the main Grade III-IV AE being thrombocytopenia. The significant efficacy and long-term prognostic benefit need to be determined by further follow-up.
Humans ; Middle Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Chemoradiotherapy ; Immune Checkpoint Inhibitors/therapeutic use* ; Neoadjuvant Therapy ; Prospective Studies ; Rectal Neoplasms/pathology* ; Thrombocytopenia/drug therapy* ; Treatment Outcome ; Adult ; Aged

OBJECTIVE: To compare the efficacy and muscle injury imaging between oblique lateral lumbar interbody fusion (OLIF) and transforaminal lumbar interbody fusion (TLIF) in the treatment of single-segment degenerative lumbar spinal stenosis. METHODS: The clinical data of 60 patients with single-segment degenerative lumbar spinal stenosis who underwent surgical treatment from January 2018 to October 2019 was retrospectively analyzed. The patients were divided into OLIF groups and TLIF group according to different surgical methods. The 30 patients in the OLIF group were treated with OLIF plus posterior intermuscular screw rod internal fixation. There were 13 males and 17 females, aged from 52 to 74 years old with an average of (62.6±8.3) years old. And 30 patients in the TLIF group were treated with TLIF via the left approach. There were 14 males and 16 females, aged from 50 to 81 years old with an average of (61.7±10.4) years old. General data including operative time, intraoperative blood loss, postoperative drainage volume, and complications were recorded for both groups. Radiologic data including disc height (DH), the left psoas major muscle, multifidus muscle, longissimus muscle area, T2-weighted image hyperintensity changes and interbody fusion or nonfusion were observed. Laboratory parameters including creatine kinase (CK) values on postoperative 1st and 5th days were analyzed. Visual analogue scale(VAS) and Oswestry disability index(ODI) were used to assess clinical efficacy. RESULTS: There was no significant difference in the operative time between two groups(P>0.05). The OLIF group had significantly less intraoperative blood loss and postoperative drainage volume compared to the TLIF group(P<0.01). The OLIF group also had DH better recovery compared to the TLIF group (P<0.05). There were no significant differences in left psoas major muscle area and the hyperintensity degree before and after the operation in the OLIF group (P>0.05). Postoperativly, the area of the left multifidus muscle and longissimus muscle, as well as the mean of the left multifidus muscle and longissimus muscle in the OLIF group, were lower than those in the TLIF group (P<0.05) .On the 1st day and the 5th day after operation, CK level in the OLIF group was lower than that in the TLIF group(P<0.05). On the 3rd day after operation, the VAS of low back pain and leg pain in the OLIF group were lower than those in the TLIF group (P<0.05). There were no significant differences in the ODI of postoperative 12 months, low back and leg pain VAS at 3, 6, 12 months between the two groups(P>0.05). In the OLIF group, 1 case of left lower extremity skin temperature increased after the operation, and the sympathetic chain was considered to be injured during the operation, and 2 cases of left thigh anterior numbness occurred, which was considered to be related to psoas major muscle stretch, resulting in a complication rate of 10% (3/30). In the TLIF group, one patient had limited ankle dorsiflexion, which was related to nerve root traction, two patients had cerebrospinal fluid leakage, and the dural sac was torn during the operation, and one patient had incision fat liquefaction, which was related to paraspinal muscle dissection injury, resulting in a complication rate of 13% (4/30). All patients achieved interbody fusion without cage collapse during the 6- month follow-up. CONCLUSION Both OLIF and TLIF are effective in the treatment of single-segment degenerative lumbar spinal stenosis. However, OLIF surgery has obviously advantages, including less intraoperative blood loss, less postoperative pain, and good recovery of intervertebral space height. From the changes in laboratory indexes of CK and the comparison of the left psoas major muscle, multifidus muscle, longissimus muscle area, and high signal intensity of T2 image on imaging, it can be seen that the degree of muscle damage and interference of OLIF surgery is lower than that of TLIF.
Male ; Female ; Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Retrospective Studies ; Spinal Stenosis/surgery* ; Blood Loss, Surgical ; Lumbar Vertebrae/surgery* ; Spinal Fusion/methods* ; Treatment Outcome ; Pain, Postoperative ; Muscles ; Minimally Invasive Surgical Procedures/methods*

ObjectiveTo explore the possible mechanism of total flavonoids of peony flower （TFPF） in protecting rats from gouty nephropathy and provide data support for the pharmaceutical research on the treatment of gouty nephropathy. MethodGouty nephropathy rat model was established by adenine combined with ethambutol. Rats were randomly assigned into blank control group， model group， allopurinol （42 mg·kg^-1） group， Tongfengshu tablets （600 mg·kg^-1， positive control） group， and TFPF （260， 130， and 65 mg·kg^-1） groups. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of tumor necrosis factor-α （TNF-α）， monocyte chemoattractant protein-1 （MCP-1）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） in rat serum and those of transforming growth factor-β₁ （TGF-β₁） and IL-1β in renal homogenate. Hematoxylin-eosin（HE） staining was carried out for observation of the morphological changes of renal cells. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） was conducted for observation of the DNA damage in renal cells. The expression of NOD-like receptor protein 3 （NLRP3）， cysteine aspartic acid protease（Caspase）-1 and IL-1β were observed by immunohistochemistry. The expression levels of NLRP3， Caspase-1 and nuclear transcription factor -κB （NF-κB） in renal tissues were detected by Western blot. ResultCompared with blank group， the contents of TNF-α， MCP-1， IL-1β， IL-18， and TGF-β₁ in serum of model group were significantly increased （P<0.01）， and the expressions of NLRP3， Caspase-1， NF-κB and IL-1β in kidney of model group were significantly increased （P<0.01）. The renal tissue cells showed cytoplasmic swelling， cell membrane rupture， and the number of nuclear pyknotic fracture increased. The positive rate of TUNEL staining was significantly increased in model group （P<0.01）， and the contents of IL-1β and TGF-β₁ in renal tissue homogenate were significantly increased （P<0.01）. Compared with model group， the contents of inflammatory factors TNF-α， IL-1β and IL-18 in serum of rats in TFPF high- and medium-dose groups could be decreased to different degrees （P<0.05， P<0.01）， while the content of MCP-1 in TFPF high-dose group was significantly decreased （P<0.01）. The content of TGF-β₁ in renal tissue homogenate in TFPF high- and medium-dose groups was significantly decreased （P<0.05， P<0.01）， and the content of IL-1β in renal tissue homogenate in TFPF medium-dose group was significantly decreased （P<0.01）. HE staining showed that each dose group of TFPF could improve the status of renal tubular epithelial cells， reduce cytoplasmic swelling and the number of nuclear pyknosis to varying degrees. The positive rate of TUNEL staining was decreased （P<0.01） and DNA damage was decreased. The expression of NLRP3， Caspase-1， IL-1β and NF-κB protein in renal tissue cells was inhibited （P<0.05， P<0.01）. ConclusionTFPF protects rats from gouty nephropathy by inhibiting the secretion of inflammatory cytokines. Specifically， it may inhibit the activation of NF-κB and NLRP3/Caspase-1 pathways to reduce the expression， maturation， and release of inflammatory cytokines such as IL-1β and IL-18 and further inhibit pyroptosis， thereby reversing the inflammatory injury of kidney in gouty nephropathy.

Objective:To explore the macroscopic medication rule of Chinese medicine for the treatment of primary liver cancer and provide references for clinical medication. Method:The databases of CNKI，VIP， and Wanfang Data were searched for research articles published from September 1959 to June 2019 with the terms of "Chinese medicine" and "liver cancer". A database was established based on the collected Chinese medicinal prescriptions for the treatment of primary liver cancer. The frequency，clustering， and association rules were analyzed by Excel， etc. Result:In this study，106 effective articles were included，and after the modified prescriptions were removed， 92 effective prescriptions were screened out，involving 281 Chinese herbal medicines used for 1 181 times in total. The top 5 high-frequency drugs were Poria （deficiency-tonifying），Astragali Radix （heat-clearing），Bupleuri Radix （blood-activating and stasis-resolving），Paeoniae Radix Alba （urination-promoting and dampness-draining）， and Codonopsis Radix （Qi-regulating）. The analysis of drug flavor with a frequency higher than 10 showed that most of the drugs were sweet，bitter， and pungent in flavor，cold，warm， and plain in nature，and acted on spleen and liver meridians. Four combinations and 10 herbal pairs were obtained by the cluster analysis of high-frequency drugs and association analysis， respectively. The high-frequency drugs and potential herbal pairs were classified targeting the specific clinical syndromes in different stages of liver cancer. Conclusion:Replenishing Qi， invigorating spleen，clearing heat， removing toxin，activating blood， and resolving stasis were the basic principles for the treatment of primary liver cancer. The combination of those drugs was the main therapeutic strategy. In addition，the resulting 10 potential herbal pairs from high-frequency drugs and cluster analysis could inspire the clinical treatment of primary liver cancer in different clinical stages with various clinical syndromes， which was of reference value for the clinical medication.

Moxa smoke plays an indispensable role in traditional Chinese medicine with the functions of dispelling poison, exorcizing evil and avoiding filth, dispelling cold, etc. It has been used to prevent pestilence for thousands of years. This paper reviewed the clinical application, mechanism and existing shortcomings of moxa smoke for preventing epidemic diseases, and found that moxa smoke can effectively inhibit a variety of pathogenic bacteria, fungi and viruses that cause infectious and epidemic diseases, and has good pharmacological effects of sterilization, antiviral and immunity enhancement, and has achieved remarkable effect in disease prevention, health care and plague prevention. It is suggested that attention should be paid to the air quality of moxibustion clinics in the future, it is urgent to establish a unified sanitary air quality standard system to create a good clinic environment. At the same time, the research on the clinical safe concentration range of moxa smoke should be strengthened to effectively avoid the occurrence of adverse reactions, give full play to the efficacy of moxa smoke in eliminating pathogenic factors and preventing epidemic, so as to provide the basis for the rational application and promotion of moxa smoke.

In recent years,the safety of " toxic" traditional Chinese medicine has received great attention. Similarly,the safety of " toxic" Chinese medicines for external use should not be ignored. In this paper,the adverse reactions of toxic Chinese medicine for external use were systematically studied; the causes for adverse reactions were analyzed; and the key problems on the external use of toxic Chinese medicine in modern clinical practice were put forward. For example,usage dosage(time,area),specific efficacy of external use,early warning index of toxicity,toxic dose,adverse effects,toxic symptoms and corresponding treatment measures all had no reference basis,lacking a systematic toxicity evaluation medication criteria for clinical external use of toxic Chinese medicine. Attention shall be paid to the toxicity of toxic Chinese medicine for external use,and the theory of toxicity evaluation should be established for the external use of " toxic" traditional Chinese medicine under specific conditions. The early warning mechanism for toxic and adverse effects were clarified,and relevant early warning sensitive indicators applicable to clinical use were established in this study to control its risk factors. The study on the mechanism of pharmacodynamics and toxicology of " toxic" traditional Chinese medicine for external use was strengthened to clarify the usage and specific effects of external use. On the basis of this,the study of synergism and reduction of toxicity was carried out to maximize the efficacy of external use of traditional Chinese medicine under specific conditions. A toxicity standard of " toxic" Chinese medicines for external use was put forward,which was of great significance to guide clinical safety,rationality,effectiveness as well as the research and development of new dosage forms for external use of traditional Chinese medicine.
Drug-Related Side Effects and Adverse Reactions ; Drugs, Chinese Herbal ; toxicity ; Humans ; Medicine, Chinese Traditional ; Research

Cells, Cultured ; Cyclic Nucleotide Phosphodiesterases, Type 2 ; antagonists & inhibitors ; metabolism ; Fibroblasts ; drug effects ; metabolism ; Glucosides ; pharmacology ; Humans ; Lung ; cytology ; embryology ; Phenols ; pharmacology ; Phosphodiesterase Inhibitors ; pharmacology ; Tumor Suppressor Protein p53 ; metabolism

Through analysis of factors affecting toxicity of traditional Chinese medicine (TCM), relationship between toxicity of TCM and physical constitution was explored, which provided a new idea for preventing occurrence of toxicity of TCM. Efforts were made to summarize causes of toxicity of TCM, and analyze relationship between physical constitution and toxicity of TCM. following aspects were taken into account:①main reason for people to use TCM is disease, which is pathological state of human beings. The pathological state may have more demands for corresponding TCM. The TCM rule of "disease-based treatment" is an important manifestation for correlating drugs with syndromes. Then how can normal animals reflect human toxicity under pathological conditions. ②People with pathological conditions, especially with a long disease course, may have abnormal liver and kidney functions. Then how to distinguish cause of toxicity of TCM in liver and kidney dysfunctions.③The long-term disease state can also lead to disorder of intestinal flora of body. Then how is impact of interaction between intestinal flora and TCM reflected in toxicity of TCM.④Although emotional and psychological factors account for a small proportion of toxicity of TCM, it still has an effect.⑤Although humans and animals have a high degree of similarity, there are still species differences (such as croton). Then how is human clinical toxicity consistent with animal research toxicity. The efficacy is related to expectation, while toxicity is related to background. At present, toxicity of TCM is more caused by factors of TCM (such as variety, quality, processing), and factors of TCM application (like compatibility, drug correspondence, dosage, course of treatment), which are external causes of toxicity of TCM. physiological condition, pathological state, emotional and psychological factors, and intestinal flora of body are internal factors. The physical constitution factors are internal factors of toxicity of TCM, and external factors play a role based on internal factors. At the same time, there are essential differences between humans and animals. Animal toxicological experiments are only for clinical reference. By analyzing concepts related to toxicity of TCM and physical constitution factors, modern researches on toxic effects of TCM are also promoted accordingly, and TCM toxicity theory is also improved, which provides a scientific basis for safe and rational application of TCM in clinical practice. Of course, research on animal models under pathological conditions shall be strengthened to promote study of toxicity of TCMs, so as to deepen people's understanding of toxicity of TCMs.

Frostbite is a common disease in winter, and systemic or local injury caused by low temperature invasion. Frostbite sites are commonly face, ears, nose, hands, feet and other peripheral blood circulation parts. The main symptoms are pale skin, cold, pain and numbness, skin itching in high temperature, and severe cases may suffer from skin erosions and ulcers. Frostbite model is a pathological model mainly based on Western medicine index. Based on the analysis of clinical symptoms of frostbite in traditional Chinese medicine and western medicine, and a large number of experimental studies on the existing animal models, the animal model preparation of specifications (draft) was formulated as follows.
Animals ; Cold Temperature ; Frostbite ; Models, Animal